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961.
Martínez MA Rincón A Desviat LR Merinero B Ugarte M Pérez B 《Molecular genetics and metabolism》2005,84(4):317-325
Isolated methylmalonic aciduria (MMA) is an inborn error of metabolism due to the impaired isomerization of l-methylmalonyl-CoA to succinyl-CoA. This reaction is catalyzed by the mitochondrial protein methylmalonyl-CoA mutase (MCM, EC 5.4.99.2), an adenosylcobalamin-dependent enzyme. Four different forms of isolated MMA have been described: mut MMA associated with defects in the MCM apoenzyme, and phenotypically divided into two subtypes mut- and mut0 MMA, and three different defects involved in the synthesis of the active form of the cofactor adenosylcobalamin, termed cbl MMA, and classified into three different complementation groups cblA, cblB, and cblH associated with defects in the MMAA and MMAB genes and with an unidentified protein, respectively. In this work we describe the genetic analysis of 25 MMA patients, mainly from Spain. Using biochemical and cellular approaches our patients have been classified, identifying 13 mut MMA, 7 cblA, 2 cblB, and 3 noncblA, noncblB deficient patients. cDNA and genomic DNA sequence analysis of the MUT, MMAA, and MMAB genes have allowed us to identify 27 different changes, 21 novel ones. Among the missense mutations identified in the MUT gene only one, the c.970G>A (p.A324T) variant located in the substrate binding domain is likely a mut- mutation. The remaining missense mutations c.326A>G (p.Q109R), c.983T>C (p.L328P), c.1846C>T (p.R616C), and c.1850T>G (p.L617R) are probably mut0. In the MMAA patients analyzed, frameshift mutations are prevalent. We have explored the genotype-phenotype correlation for this clinically heterogeneous disease. 相似文献
962.
Involvement of the dorsolateral funiculus in the descending spinal projections responsible for diffuse noxious inhibitory controls in the rat 总被引:1,自引:0,他引:1
Recordings were made from convergent neurons in the lumbar dorsal horn of the spinal cord of the rat. These neurons were activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields located on the extremity of the hindpaw. Transcutaneous application of suprathreshold 2-ms square-wave electrical stimuli to the center of the excitatory field, resulted in responses to C-fiber activation being observed. This type of response was inhibited by applying a noxious thermal conditioning stimulus on the muzzle. The immersion of the muzzle in a 52 degrees C waterbath resulted in a strong reduction of the response during the application of the noxious conditioning stimulus and this was followed by long lasting poststimulus effects. Such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects on these inhibitions of lesions including the dorsolateral funiculus (DLF) were investigated in acute experiments: tests were performed before and at least 30 min after the DLF lesion. A lesion including the DLF ipsilateral to the neuron under study completely abolished the inhibitory processes triggered from the muzzle. Concomitantly, a facilitation of C-fiber responses was observed. Nevertheless, DNIC was still impaired even using a juxtathreshold current to elicit a weak C-fiber response. To ascertain further the main, if not entire, participation of the ipsilateral DLF in the descending projections responsible for the heterotopic inhibitory processes, the effects of a lesion of the contralateral DLF were investigated. Neither the inhibitory processes nor the unconditioned C-fiber responses were altered by this procedure. Again, a second lesion including the ipsilateral DLF induced a blockade of DNIC. It is concluded that the descending projections involved in the triggering of DNIC are mainly, if not entirely, confined to the DLF ipsilateral to the neuron under study. The contralateral DLF did not appear to play a role in these processes. 相似文献
963.
D Le Bars L Villanueva D Bouhassira J C Willer 《Patologicheskaia fiziologiia i èksperimental'naia terapiia》1992,(4):55-65
Some neurones in the dorsal horn of the spinal cord are strongly inhibited when a nociceptive stimulus is applied to any part of the body, distinct from their excitatory receptive fields. This phenomenon was termed "Diffuse Noxious Inhibitory Controls" (DNIC). DNIC influence only convergent neurones: the other cell types which are found in the dorsal horn, including specific nociceptive neurones, are not affected by this type of control. In normal conditions, these inhibitions can be triggered only by conditioning stimuli which are nociceptive. The inhibitions are then extremely potent, affect all the activities of the convergent neurones and persist, sometimes for several minutes, after the removal of the conditioning stimulus. In fact, only activity of A delta- or A delta- and C-peripheral fibres can trigger DNIC. DNIC are sustained by a complex loop which involves supraspinal structures since, unlike segmental inhibitions, they can not be observed in animals in which the cord has previously been transsected at the cervical level. The ascending and descending limbs of this loop travel respectively through the ventro-lateral and dorso-lateral funiculi respectively. We proposed that DNIC result from the physiological activation of some brain structures putatively involved in descending inhibition. However, lesions of the following structures did not modify DNIC: Periaqueductal grey (PAG), Cuneiform nucleus, Parabrachial area, locus coeruleus/subcoeruleus, rostral ventromedial medulla (RVM) including Raphe Magnus, Gigantocellularis and Paragigantocellularis nuclei. By contrast, lesions of Subnucleus Reticularis Dorsalis (SPD) in the caudal medulla strongly reduced DNIC. Both electrophysiological and anatomical data support the involvement of SRD neurones in spin-bulbo-spinal loop(s). Indeed, they are unresponsive to visual, auditory or proprioceptive stimulation but are preferentially or exclusively activated by nociceptive stimuli with a "whole-body receptive field"; they encode precisely the intensity of cutaneous and visceral stimulation within the noxious range and are exclusively activated by cutaneous A delta- or A delta- and C-fibre peripheral volleys; they send descending projections through the dorsolateral funiculus that terminate in the dorsal horn at all levels of the spinal cord. In man, exactly analogous results have been obtained by means of combined psychophysical measurements and recordings of nociceptive reflexes. Electrical stimulation of the sural nerve at the ankle simultaneously induces a nociceptive reflex in a flexor muscle of the knee (the RIII reflex) and a painful sensation from the territory of the nerve. Painful heterotopic conditioning stimuli, no matter whether thermal, mechanical or chemical in nature, depress both the reflex and the associated painful sensation, with stronger effects being observed with more intense conditioning stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
964.
García Páez JM Carrera Sanmartin A Jorge Herrero E Millán I Cordón A Rocha A Maestro MA Burgos R Téllez G Castillo-Olivares JL 《Journal of biomedical materials research. Part B, Applied biomaterials》2005,72(1):9-16
We studied the mechanical behavior in response to tensile stress of samples of ostrich pericardium bonded with a cyanoacrylate glue or sewn with a rectangular, overlapping suture that was subsequently sealed with the same bioadhesive. Seventy-two trials were performed in three series of 24 samples each: series AG, glued with an overlap of 1 cm2; series ASG, sewn with a rectangular, overlapping suture and sealed; and series AC, control samples that were left intact. The mean stress at rupture in series AG (glued) was 0.1 MPa, much lower than the working stress of a human valve leaflet, which is approximately 0.25 MPa. In the control series, this stress was 26.28 MPa. At rupture in series ASG (sutured/glued), the suture material was being subjected to a stress of 64.91 MPa, thus confirming the existence of an interaction between the suture and the shear stress exerted by the suture on the samples of pericardium. In series ASG, the mean value for the resistance to rupture when measured in machine kg was 8.83 kg, lower than but similar to that recorded in the control series AC (10.26 kg). The percentages of reversible deformation, or elongation, once the samples were torn were similar in series AC (19.15%) and ASG (21.93%). This phenomenon can only be explained by the damage to the collagen fibers in the area around the rupture, while other more distant regions work at a lower load within the elastic limit. We conclude that cyanocrylate adhesives alone are not suitable as bonding materials in cardiac bioprostheses. The results with the rectangular, overlapping suture, when subsequently sealed with an adhesive, can be considered good because, although this approach does not impede shear stress, it does maintain an excellent degree of resistance to rupture of the samples thus joined. We stress the need to take into account the concentration of the load in the design of bioprostheses. 相似文献
965.
A search via the literature and two new studies for factors predictive of falling by psychiatric inpatients 50 years and older revealed the following. Comparison in an initial study of patients who had fallen with control patients who had not fallen demonstrated little clearcut difference in regard to possible effects of 64 variables. A second, larger study showed that patients who fell did not differ significantly from the general population of hospital inpatients 50 and older in regard to age, sex, particular hospital unit, or use of tricyclic antidepressants and neuroleptics. 相似文献
966.
Total HCV core antigen assay. A new marker of HCV viremia and its application during treatment of chronic hepatitis C 总被引:2,自引:0,他引:2
Lorenzo J Castro A Aguilera A Prieto E López-Calvo S Regueiro B Pedreira J 《Journal of virological methods》2004,120(2):173-177
The present study assesses the clinical usefulness of the hepatitis C core antigen assay for monitoring of patients being treated for chronic hepatitis C virus (HCV) infection. Eighty-six serum samples were selected at random from 16 patients and levels of HCV RNA and HCV core antigen were determined simultaneously and in parallel to compare both techniques. The data obtained were compared by Pearson’s correlation and the coefficients calculated by Fisher transformation and by calculating the difference and standard error. A good linear correlation was observed between both techniques. Maximum correlation, with significant difference, was found between patients infected with the 1a genotype and other genotypes. In conclusion, the HCV core antigen assay is useful for the diagnosis of early infection; however, its use for determining the exact timing of viral elimination during treatment is clearly unsuitable. 相似文献
967.
Comparative Study of Bacteremias Caused by Enterococcus spp. with and without High-Level Resistance to Gentamicin 总被引:3,自引:0,他引:3
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Francisco Javier Caballero-Granado J. M. Cisneros R. Luque M. Torres-Tortosa F. Gamboa F. Díez J. L. Villanueva R. Prez-Cano J. Pasquau D. Merino A. Menchero D. Mora M. A. Lpez-Ruz A. Vergara for the Grupo Andaluz Para El Estudio De Las Enfermedades Infecciosas 《Journal of clinical microbiology》1998,36(2):520-525
A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections. 相似文献
968.
969.
Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla. 总被引:1,自引:0,他引:1
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1. In anaesthetized rats, recordings were made in the medullary subnucleus reticularis dorsalis. Neurones with total nociceptive convergence (TNC) responded to percutaneous electrical stimuli with early and late peaks due to the activation of A delta and C fibres respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence (PNC) responded with an A delta peak regardless of which part of the body was stimulated, and with a C peak of activation from some, mainly contralateral, parts of the body. 2. All TNC neurones responded to noxious thermal stimulation of the limbs with a phasic discharge followed by tonic activity that lasted throughout the stimulation. Discharges elicited by applying stimuli simultaneously to both forepaws or to a hindpaw and a forepaw were lower than the individual responses to stimulation of a single limb. Similar negative interactions were observed in the responses of PNC neurones following noxious thermal stimulation of two paws. 3. In both neuronal populations, the simultaneous application of noxious thermal stimuli and microelectrophoretic application of D,L-homocysteic acid (DLH) induced responses of greater magnitude than those evoked by each stimulus alone. 4. TNC neurones responded to electrical stimulation of the contralateral hindpaw with A delta and C fibre responses. Noxious thermal stimuli applied to different areas of the body induced an excitatory response during the period that preceded the electrical stimulation, but an inhibition of both A delta and C fibre responses. By contrast, using a similar protocol, application of DLH induced a steady discharge in the period preceding the electrical stimulation and also in between the A delta and C fibre responses, which were not themselves inhibited. 5. The negative heterotopic influences in normal rats during simultaneous immersion of the ipsi- and contralateral hindpaws was strongly reduced in rats with bilateral lesions of the dorsolateral funiculi at the cervical level (C3-C4). 6. It is concluded that strong negative interactions elicited by heterotopic noxious stimuli are observed in the spinoreticular system. Such interactions do not occur at the subnucleus reticularis dorsalis level but are mediated by supraspinal structures which control, through the dorsolateral funiculi, the spinal transmission of nociceptive information. 相似文献
970.
Increased CD8+-T-Cell Expression and a Type 2 Cytokine Pattern during the Muscular Phase of Trichinella Infection in Humans 总被引:2,自引:0,他引:2
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Maria Angeles Gomez Morales Raffaella Mele Massimo Sanchez Daria Sacchini Marzia De Giacomo Edoardo Pozio 《Infection and immunity》2002,70(1):233-239
Cell-mediated immunity during the muscular phase of Trichinella infection in humans was studied. Cell proliferation, the phenotypic changes in the T-cell population, and expression and production of cytokines were examined by using peripheral blood mononuclear cells (PBMC) collected at different times postinfection from 10 individuals who had acquired Trichinella spiralis and five individuals who had acquired Trichinella britovi in two distinct outbreaks. T. spiralis and T. britovi crude worm extracts induced proliferation of PBMC from T. spiralis- and T. britovi-infected donors. Cytokine gene expression showed a predominant type 2 pattern for the entire period of infection studied, although gamma interferon (IFN-gamma) was expressed. Interleukin-2 (IL-2), IL-5, IL-10, and IFN-gamma production was found in PBMC of all donors. There was a good correspondence between the cytokine expression and production patterns. Changes in PBMC composition, with a trend toward an increase in CD8(+) lymphocyte counts, were observed. 相似文献